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oai:recercat.cat:11351/77802025-10-24T10:33:25Zcom_2072_378070com_2072_378040col_2072_378092

A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Cancer Byers, Lauren Averett Navarro Mendivil, Alejandro Schaefer, Eric Johnson, Melissa L. Han, Ji-Youn Özgüroglu, Mustafa Institut Català de la Salut [Byers LA] University of Texas MD Anderson Cancer Center, Houston, TX. [Navarro A] Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Schaefer E] Highlands Oncology Group, Fayetteville, AR. [Johnson M] Sarah Cannon Research Institute, Nashville, TN. [Özgüroğlu M] Istanbul University–Cerrahpaşa, Istanbul, Turkey. [Han JY] National Cancer Center, Goyang-si Gyeonggi-do, South Korea Vall d'Hebron Barcelona Hospital Campus Pulmons - Càncer - Tractament Proteïnes quinases - Inhibidors Avaluació de resultats (Assistència sanitària) DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia Checkpoint kinase 1 inhibitor; Pharmacokinetics; Small cell lung cancer Inhibidor de quinasa de punto de control 1; Farmacocinética; Cáncer de pulmón de células pequeñas Inhibidor de la quinasa del punt de control 1; Farmacocinètica; Càncer de pulmó de cèl·lules petites Background This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage small-cell lung cancer (ED-SCLC). Patients and Methods This was a parallel-cohort phase II study of 105 mg/m2 prexasertib once every 14 days for patients who progressed after no more than two prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternative regimen (Cohort 3: 40 mg/m2 days 1-3, 14-day cycle). Results In Cohort 1 (n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [CI], 1.31-1.64); and median OS, 5.42 months (95% CI, 3.75-8.51). In Cohort 2 (n = 60), ORR was 0%; DCR, 20%; median PFS, 1.36 months (95% CI, 1.25-1.45); and median OS, 3.15 months (95% CI, 2.27-5.52). The most frequent all-grade, related, treatment-emergent adverse events were decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified. Conclusion Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC. This research was funded by Eli Lilly and Company. 2022-07-18T10:19:00Z 2022-07-18T10:19:00Z 2021-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Byers LA, Navarro A, Schaefer E, Johnson M, Özgüroğlu M, Han JY, et al. A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-stage Small-cell Lung Cancer. Clin Lung Cancer. 2021 Nov;22(6):531–40. 1525-7304 https://hdl.handle.net/11351/7780 10.1016/j.cllc.2021.04.005 34034991 000723160600005 http://hdl.handle.net/11351/7780 eng Clinical Lung Cancer;22(6) https://doi.org/10.1016/j.cllc.2021.04.005 Attribution-NonCommercial-NoDerivatives 4.0 International Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier Scientia